Ferrographic apparatus

ABSTRACT

A ferrographic apparatus and method incorporate a priming operation that moves a priming fluid, in a direction opposite to the flow direction subsequently followed by the sample fluid, through a fluid pathway including the flow chamber. The fluid pathway is configured to facilitate dissipation of any gas bubble introduced into it during the priming operation and to reduce adventitious deposition of specimen material at locations other than the substrate. Sample fluid to be analyzed is added to the reservoir so as to form a bubble-free interface with the priming fluid, and the direction of movement through the flow chamber is reversed. The resulting continuous fluid column is advanced through the fluid pathway so that the sample fluid enters the flow chamber through the inlet port and passes through the magnetic field gradient, exiting through an orifice at the opposite end of the flow chamber serving as the outlet port. The flow chamber of the ferrograph is preferably contained in a deposition cassette comprising the substrate, a gasket and a platen which incorporates an integral fluid reservoir in communication with the inlet port. A pump is preferably configured to move each liquid through the fluid pathway at a distinct flow rate and in a direction according to the function performed by the respective liquid.

This application is a divisional of and claims benefit of prior U.S.Ser. No. 09/082,067 filed on May 20, 1998 now U.S. Pat. No. 6,156,208.

BACKGROUND OF THE INVENTION

Ferrography is a method of separating suspended particles displayingmagnetic properties from a liquid by passing the liquid through amagnetic field. The interaction between the magnetic field through whichthe particles move and the magnetic dipole moments of the particlescauses the particles to deposit onto a substrate in the region ofstrongest field gradient. This approach, applied to removing wearparticles from used lubricating oil, was first described in U.S. Pat.No. 4,047,814, herein incorporated by reference.

Ferrographic techniques have also been applied to cell sorting methodsthat exploit differences in surface protein compositions of biologicalcells, such as find wide application in research and in diagnosticprocedures relating to cancer and immunodeficiency diseases, as well asin other biomedical applications. This type of analysis is based on theability of magnetic tags conjugated to appropriate antibodies to attachto specific surface protein compositions. For example, after magnetictagging, lymphocytes may be readily sorted ferrographically. Thisapproach to cell sorting efficiently concentrates the cells of interestand thus does not require sophisticated fluidic or optical systems forsubsequent study or counting of the cells.

U.S. Pat. No. 5,714,059, herein incorporated by reference, discloses ananalytical ferrograph, also called an analytical magnetic cytometer,suitable for magnetically driven cell deposition. Its magnet has polemembers defining an interpolar gap therebetween with a relatively highmagnetic flux density. For ferrographic analysis of biological cellssuspended in a sample fluid, an aliquot of the sample fluid is passedthrough a liquid-tight flow pathway, including a flow chamber which ispart of a larger flow unit, disposed in the fringing magnetic field. Inthe flow chamber, this flow pathway is defined by opposing parallelplates, one of which, the substrate, is mounted against the pole membersand over the gap. Particles that are magnetically susceptible (eithernaturally or due to prior preparation by techniques well known to thoseskilled in the art) are separated from the balance of the sample fluid,and are deposited onto a deposition surface, i.e., the interior surfaceof the substrate, facing away from the pole gap. After the entirealiquot has passed through the flow chamber, the flow unit isdisassembled and the deposit is analyzed.

A flow chamber in the flow unit is defined by a hole through a spacersheet, or gasket, of elastomeric material disposed between the twoplates, one of which is the substrate and the other of which is referredto herein as the platen. Pressure applied perpendicularly to thesubstrate surface maintains the integrity of the seal around each flowchamber. Or, electrostatic or frictional forces can hold the platesagainst the spacer sheet, parallel to one another. Free ends of thesheet extending beyond the edges of the substrate and platen facilitatedisassembly of the unit without disruption of the substrate or deposit.

A flow unit including several parallel flow chambers, each defined by ahole through the gasket, is used to permit simultaneous processing ofseveral aliquots under identical flow and magnetic field conditions.Collection of the resulting deposits in compact form on a singledeposition surface facilitates comparison of different deposits derivedfrom the same fluid source.

Several features of the flow unit promote optimal performance of such asystem. Typically, the substrate onto which the cells are deposited is athin slide of common borosilicate glass. The optical transparency,mechanical rigidity, smooth surface, and low chemical reactivity ofglass facilitate analysis of the deposit after removal of the flowchamber from the apparatus. A very thin substrate—preferably on theorder of 100 micrometers—allows the deposition surface to be as close aspossible to the interpolar gap so that tagged cells in the fluid flowingadjacent the gap encounter strong field gradients which efficiently drawthe cells to the surface, where they are deposited in compact,well-defined regions. Finally, the flow unit is economically disposableafter a single use to satisfy hygienic requirements.

Although known ferrographic systems effectively separate biologicalcells, several characteristics of past fluid pathway implementationshave limited their serviceability. For example, to form a fluid pathway,thin tubing is typically joined to the flow unit at two orifices in theplaten which serve as ports for a single flow chamber. As the samplefluid passes through such a pathway, surface irregularities—such asdiscontinuities, crevices or diameter changes—along the length of tubingand especially at the joints, induce suspended material, includingmagnetically tagged bodies of interest, to be caught and remain at theseunintended deposition sites. Specimen matter is lost in greater quantitywith an increase in the tubing length or the number and/or abruptness ofdiameter changes experienced by the sample fluid before it reaches thedesired deposition site on the substrate. Processing protocols entailingmoving the sample fluid through the flow chamber in one direction andthen reversing the flow direction to pass the same fluid through theflow chamber a second time also are predisposed to loss of specimenmatter.

Another difficulty with known systems is related to the processing ofseveral fluids. The aliquot of sample fluid is typically followedthrough the fluid pathway by one or more additional liquids in order tointeract with material deposited on the substrate. For example, one suchliquid may stain deposited cells to facilitate their visual examination.A rinse fluid may then be applied to remove extraneous stain materialor, even if no stain is applied in situ, to reduce the number ofnonmagnetic elements entrained in the deposit. Such a multi-fluidsequence is often implemented by consecutively disposing the severalliquids in one of the lengths of tubing and then moving the liquidsthrough the flow chamber. Gas bubbles at the interfaces between adjacentfluids collect in the flow chamber, interfering with deposition ofspecimen material. The total amount of sample fluid that can beconveniently processed is limited by the tubing volume. The surfaceirregularities and extended distance which the interface betweenadjacent fluids traverses dispose the fluids to premature anduncontrolled mixing which, in the case of a staining liquid followingthe sample fluid, impairs control of the staining operation.

DESCRIPTION OF THE INVENTION OBJECTS OF THE INVENTION

It is, accordingly, an object of the invention to provide a ferrographicapparatus and method that allows processing of a sample fluid withoutintroducing bubbles into the fluid pathway.

It is another object of the invention to provide such an apparatus andmethod capable of processing arbitrarily large sample volumes.

It is yet another object of the invention is to provide such anapparatus and method that reduces the loss of specimen material byunintended deposition of suspended material before it passes through themagnetic field.

It is yet another object of the invention to provide such an apparatusand method capable of capturing cells present in a sample fluid at verylow concentrations.

It is yet another object of the invention to provide such an apparatusand method capable of consecutively processing several fluids withoutintroducing gas bubbles into the fluid pathway, and with minimal mixingtherebetween.

Yet another object of the invention is to provide such an apparatus andmethod that affords improved exposure control of specimen materialdisplaying magnetic properties to staining agents.

Another object of the invention is to provide such an apparatus andmethod that minimizes subjection of the specimen materials todestructive conditions, such as passage through a peristaltic pump,before they pass through the flow chamber.

It is another object of the invention to provide such an apparatus andmethod capable of efficiently removing extraneous material from thedeposit.

BRIEF SUMMARY OF THE INVENTION

The invention provides a ferrographic apparatus and method that enablethe production of deposits of consistent quality by an uncomplicatedspecimen handling procedure. The system of the invention incorporates apriming operation that moves a priming fluid, in a direction opposite tothe flow direction subsequently followed by the sample fluid, through afluid pathway including the flow chamber. The fluid pathway isconfigured to facilitate dissipation of any gas bubble introduced intoit during the priming operation and to reduce adventitious deposition ofspecimen material at locations other than the substrate.

In one aspect, the method of the invention incorporates a primingoperation that moves a priming fluid slowly into the flow chamber untilits meniscus has left the flow chamber through an orifice in the platenserving as an inlet port at one end of the flow chamber. Any gas bubbletraveling with the priming fluid meniscus is displaced through the inletport into a reservoir. The reservoir is preferably of sufficientdiameter to allow any bubble at the liquid surface to readily burst. Thesample fluid to be analyzed is then added to the reservoir so as to forma bubble-free interface with the priming fluid, and the direction ofmovement through the flow chamber is reversed. The resulting continuousfluid column is advanced through the fluid pathway so that the samplefluid enters the flow chamber through the inlet port and passes throughthe magnetic field gradient, exiting through an orifice at the oppositeend of the flow chamber serving as the outlet port.

If additional fluid, such as extra sample fluid or a staining or rinsingsolution, is to be passed through the flow chamber, it is added to thereservoir before the sample fluid meniscus has reached the inlet port inorder to form a bubble-free interface with the fluid already in thereservoir. Each fluid addition is similarly introduced by placing itinto the reservoir so as to form an interface with the liquid precedingit. In one embodiment the reservoir is open to the atmosphere so thatadditional fluid can be introduced by pipette. In another embodiment,the reservoir is capped and functions as a drip chamber for a largervessel of fluid. Fluid may be added to the top of the reservoir as it isbeing drawn into the chamber from the bottom; or, the fluid column maybe static during fluid additions. In any of these cases, the capacity tocontinually add fluid to the reservoir allows arbitrarily large fluidvolumes, much greater than the reservoir volume to be processed.

In another aspect, the flow chamber of the ferrograph of the inventionis contained in a deposition cassette comprising the substrate, a gasketand a platen which incorporates an integral fluid reservoir incommunication with the inlet port. Including the reservoir in thedeposition cassette eliminates surface discontinuities present at aninlet port-tubing joint and reduces the length of the fluid pathwaytraversed by the sample fluid. Both of these attributes minimizeopportunity for adventitious deposition, which affords the invention agreater capture efficiency and suits the cassette for the analysis ofcells present at very low concentrations. The integral reservoir andshort pre-flow chamber promote the preservation of a relatively sharpinterface between different consecutive liquids; such an interfaceremains substantially intact during movement through the fluid pathway,with any mixing across the interface occurring over an insignificantdistance compared to the total length in the fluid column of the fluidsforming the interface, so that the exposure of the matter in one of theliquid to matter in the other of the liquids does not occur in anuncontrolled fashion. The reservoir is preferably tapered to broadenaway from the inlet port so that a diameter sufficient for bubbledissipation is realized without any abrupt diameter changes. Thedeposition cassette of the invention is compact and convenient for theuser; once the assembled cassette is loaded into the ferrograph, nofurther connections to the inlet port are necessary in order to addfluid to the reservoir.

These two aspects are especially advantageous in combination in thatthey permit the serial processing of several fluids without theintroduction of bubbles or significant mixing therebetween. Theinvention achieves this functionality without a complex system of valvesfor feeding distinct liquids into the system.

An outlet conduit in communication with the outlet port receives fluidleaving the flow chamber. A pump operating on the outlet conduitcontrols the movement of fluid through the fluid pathway. The locationof the outlet port-conduit joint and of the pump downstream from thedeposition chamber protects the specimen cells respectively fromunintended deposition sites and from potentially destructive mechanicalaction before exposure to the magnetic field.

In another aspect of the invention, the pump is configured to move eachliquid through the fluid pathway at a distinct flow rate and in adirection according to the function performed by the respective liquid.For example, the pump may force priming fluid into the reservoir at amoderate priming rate, then reverse direction to draw sample fluidthrough the flow chamber at a slower sample fluid rate, and finally usea much greater rate, for example 10, 20, 50 or 100 times the samplefluid rate, for rinsing. The sample fluid rate is chosen to allow thespecimen material sufficient residence time in the flow chamber to bedeposited on the substrate; a high rinsing rate provides force adequateto efficiently remove entrained nonmagnetic material while the specimenmaterial of interest is held securely on the substrate by the magneticfield. A staining solution following the sample fluid may be moved alongthe fluid pathway at zero velocity—that is, allowed to remain stationaryin the flow chamber—for a fixed length of time in order to regulate theinteraction between the deposit and the staining agent.

In one embodiment, the deposition cassette is removed from theferrograph before rinsing so that, free from the restraining force ofthe magnetic field, the deposit is flushed off the substrate and out ofthe chamber. Such a flushing step may be preceded by a rinse fluidcontaining an enzymatic agent that acts to alter the bond between thedeposited material and the substrate so as to facilitate removal of thedeposit by flushing. Any of the staining, rinsing, or flushing steps maybe applied selectively to some or all of the flow chambers of amulti-chambered cassette.

The language of this description is not intended to limit the inventionto the treatment of biological cells but rather is directed in generalto the separation of suspended magnetic particulate matter from a fluid,be the particulate matter, for example, organic, inorganic, geological,or colloidal in nature. As used herein, the phrase “a materialdisplaying magnetic properties” includes ferromagnetic, paramagnetic,superparamagnetic and diamagnetic materials. Thus, the invention may beused to expose a suspended diamagnetic material to a magnetic fieldgradient so as to repel it from the substrate, thereby effectingseparation of the diamagnetic material from other material in the fluid.Also, although the invention is sometimes described herein in terms of asingle-flow-chamber deposition cassette, the invention also encompassesflow units accommodating several parallel flow chambers.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention description below refers to the accompanying drawings, inwhich identical reference numerals refer to the same component, ofwhich:

FIG. 1 shows a deposition cassette of the invention in exploded view;

FIG. 2 schematically depicts a ferrograph incorporating the depositioncassette of FIG. 1

FIG. 3A is a photograph showing ferrographically deposited leukocytesstained and rinsed in situ using a high rinsing flow rate;

FIG. 3B is a photograph of ferrographically deposited leukocytes stainedand rinsed by dipping the substrate respectively in staining and rinsingsolutions; and

FIG. 4 schematically depicts a ferrograph in which the reservoir of thedeposition cassette functions as a drip chamber.

DETAILED DESCRIPTION OF AN ILLUSTRATIVE EMBODIMENT

The deposition cassette of the invention comprises a mutually parallelsubstrate and platen and a thin gasket of elastomeric polymer interposedbetween them, having features and dimensions as generally described inthe '059 patent. FIG. 1 shows the particular features of an illustrativeembodiment having five identical parallel flow chambers, the details ofonly one of which is indicated. The deposition cassette 20 comprises aplaten 30 and a substrate 50 with a gasket 40 interposed therebetween.The platen 30 includes a planar portion 31, which forms a seal againstthe gasket 40, and a reservoir portion including fluid reservoirs 33. Anaperture 34 in the gasket side of the platen and in fluid communicationwith the reservoir 33 serves as an inlet port for the flow chamber. Anoutlet port 35 in the gasket side of the platen 40 opens onto an outletchannel 37 at which an outlet conduit, not shown, may be attached. Thereservoir 33 preferably includes a tapered section 36 over which thediameter of the reservoir 33 increases from its value at the inlet port34 to a value sufficiently large to allow ready dissipation of gasbubbles. For most applications, the platen 30 is preferably opticallytransparent and of a relatively rigid polymeric material.

The gasket 40 is continuous except for one chamber hole 42 therethroughfor each flow chamber in the cassette 20. The inlet and outlet ports 34and 35 extend through the platen 30 over opposite ends of a chamber hole42 to provide for fluid flow through a flow chamber formed by the holein the assembled cassette. The gasket 40 is preferably of a materialthat electrostatically adheres to the platen 30 and the glass substrate50, thereby forming a conformal coating and self-sealing the peripheryof each chamber hole 42 to form a flow chamber upon slightly pressingtogether the members during assembly of the cassette 20. It is alsodesirable that the gasket material not be wet by any fluids to be usedin the flow chamber. Silicone rubber and latex rubber have provensuitable materials for the gasket 40. The gasket 40 preferably hasopposite free ends 44 extending beyond the edges of the platen 30 andsubstrate 50 to permit easy, nondestructive disassembly of the cassette20 after use. The geometry of the chamber hole 42 of the invention isnot limited to the tapered form shown; other shapes, such as ellipticalor oblong, may also be used.

FIG. 2 shows the deposition cassette 20 of FIG. 1 as it is used with aferrograph 100. The cassette 20 is mounted within a magnetic fieldestablished by a magnet structure 114. Ferrograph 100 has a fluiddispensing unit 115, such as an array of automatic pipettes controlledby a fluid dispensing control system 116, for directing a liquid intoeach of the reservoirs 33. The liquid from a reservoir eventually entersthe respective flow chamber 42 and then exits through the respectiveoutlet channel 37 and into respective outlet conduit 117. The outletconduit 117 is in communication with a fluid transport system 120 formoving liquid from a fluid source into and out of the flow chamber 42.The fluid transport system 120 includes a pump 121 for each flow chamber42, such as a syringe pump or a peristaltic pump, and may also include asource of priming fluid 122 and a pump control system 123. In apreferred embodiment, the fluid dispensing control system 116 is coupledto the fluid transport control system 123 to coordinate the delivery ofliquid into the reservoirs 33 and its removal into the flow chambers 42so that fluid remains at an appropriate level in the reservoirs 33 atall times. The fluid dispensing control system 116 and the fluidtransport control system 123 preferably control the fluid dispensingunit 115 and the fluid transport system 120, respectively, to functionindependently with respect to each of the flow chambers 42.

The magnetic structure 114 has first and second magnetic pole members132, 134 separated by an interpolar gap 146, and a magneticallypermeable support member 145. Sandwiched between the pole members andsupport member 145 are first and second permanent magnets 133, 135. Theinterpolar gap 146 is, e.g., 1.25 mm wide along the length of a flowchamber 42 and 75 mm long across the five flow chambers 42. The polemembers 132, 134 establish a magnetic flux density at the interpolar gap146 that can range up to the saturation point of the pole pieces,generally on the order of 2 Tesla.

The deposition cassette 20 is disposed in the ferrograph 100 so that theelongated flow chamber 42 extends perpendicularly across the interpolargap 146 approximately mid-way along the length of the chamber 42. Thechamber 42 is disposed in a plane generally perpendicular to the opposedfaces of pole members 132, 134, which define interpolar gap 146. The gap146 is filled with a shim of a nonmagnetic material, such as aluminum,to keep the pole members separate and thus maintain the gap 146. In thisinstance, the deposition cassette 20 is mounted so that the flowchambers 42 extend in a vertical direction. The axis 38 of the reservoirforms a 45° angle with the vertical, so the included angle of thetapered section is less than 90° to promote drainage of fluid from thetapered section 36.

Dimensions in the deposition cassette 20 are selected for compatibilitywith the structure of the particular ferrograph 100, for enhancing themagnetically driven separation, and for imparting mechanical robustnessto the cassette. For example, a ferrograph having a 0.050″ magnet gapmay use a five-chamber deposition cassette having a 0.005″ sheet ofborosilicate glass, about 1″ wide in the flow direction and 2.5″ longacross the five chambers, functioning as substrate 50; a 0.02″-thickgasket 40 of silicone rubber, about 2″ wide and 2.5″ long; and a plasticplaten with a planar portion about 1″ wide and 2.75″ long. If a thinglass sheet of the sort typically used as a cover slip for a microscopeslide is used for the substrate, the used substrate and its deposits maybe conveniently preserved and stored by mounting the used substrate on aheavier glass slide with the deposits between the substrate and themicroscope slide. An inlet port is about 0.050″ in diameter. Eachchamber hole is about 0.25″ wide and 0.625″ long in the flow direction.The flared reservoirs 33 have a maximum inner diameter of approximately0.25″.

During operation of the ferrograph, for each flow chamber 42 the fluidtransport system 120 directs priming fluid from the priming fluid sourceinto the conduit 117, through outlet channel 37 and into the flowchamber 42. The priming fluid advances until it reaches some minimumlevel 125 in the reservoir at which bubbles will readily dissipate. Thefluid dispensing control system 116 then activates the fluid dispensingunit 115 to add a first sample fluid containing suspended cellsdisplaying magnetic properties to the reservoir 33 so as to form aninterface between the priming fluid and the first sample fluid. Thefluid transport control system 123 operates the pump 121 to draw thepriming fluid, followed by the first sample fluid, back through the flowchamber 42. The liquid passes through the flow chamber 42 in a thinlaminar layer (i.e., a layer having a laminar velocity profile). Thisstrong magnetic field gradient adjacent the gap 146 of the magnetstructure 114 draws the magnetically labeled cells toward a region ofthe substrate 50 overlying the gap 146.

If desired, the fluid dispensing unit 115 is then activated to add asecond fluid, for example to rinse the deposit or impart a cytochemicalstaining agent, such as are well known to those skilled in the art, tothe reservoir 33, while some first sample fluid remains at the minimumlevel 125. The fluid transport system 120 then draws the second fluidalong the fluid pathway across the deposited cellular material on thesubstrate 50 and into the outlet conduit 117. A staining liquid may befollowed in turn by a rinsing fluid. In a preferred embodiment, thefluid transport control system is configured to move fluid through thesystem at a slower rate during cell deposition, followed by a muchfaster rate for rinsing. As illustrated in FIG. 3A, applied after insitu staining, a rinsing rate much greater than the flow rate usedduring deposition affords very efficient removal of superfluous matter200 originating in an alcohol-based stain from the deposited cells 210,especially in comparison with staining by dipping the slide in astaining solution followed by dipping in rinse solution, afterdisassembly of the deposition cassette 20, as shown by FIG. 3B.

FIG. 4 shows the deposition cassette 20 adapted for use with aferrograph 200, in which each of the reservoirs 33 is sealed with anair-tight cap 210. The fluid dispensing system comprises a refill tube220 having one end threaded through the cap 210 and extending into thereservoir 33 and the other end submerged under fluid in a bulk samplereceptacle 230 vented to the atmosphere. The fluid transport systemcomprises a syringe 250. In operation, after priming, the reservoir 33is filled with sample fluid above the minimum level 125 and then coveredby cap 210. As the syringe 250 is operated to move sample fluid throughthe flow chamber, fluid F is drawn from the receptacle 230 into thereservoir 33 so as to keep the liquid level 260 in the reservoir 33constant.

The labeled cells remaining on the substrate 50 form a characteristic“signature” band based on their relative magnetic susceptibilities. Thedeposition cassette 20 may then be removed from the magnetic structure114. The cassette 20 may be disassembled to allow microscopicobservation of the cells deposited on the substrate 50. Alternatively,the fluid delivery control system 116 and the fluid transport controlsystem 123 may operate so as to direct a fluid into at least some of theflow chambers 42 in the cassette 20 in order to flush deposited cellsinto the outlet conduit 117 so that they may be collected andresuspended for further processing. Indeed, collected cells can bealive, and cultures grown therefrom.

A multi-chambered deposition cassette 20, with a gasket 40 havingseveral chamber holes 42, is useful for performing simultaneous sortingof several portions of a bulk liquid. After assembly and loading intothe ferrograph 100, each of the resulting flow chambers 42 has arespective deposition area disposed over the interpolar gap 146. Theliquid is divided into separate aliquots, and a different cellsubpopulation magnetically marked in each aliquot. Each aliquot is fedinto a separate dispensing receptacle in the fluid dispensing system115. Liquid is directed from each dispensing receptacle into a separatereservoir 33 in the platen 30. Such a multi-chambered flow unit can beused to particular advantage where ratios of different subpopulationsare required, because simultaneous sorting of multiple cell types fromthe same sample avoids interference from extraneous experimentalvariables (e.g., temperature- and time-dependent concentration changes)that could influence results if the different cell types were sortedserially, one after another. This approach allows cells in one flowchamber of a multi-chambered cassette to be displaced out of the chamberby flushing after removing the cassette from the magnet, while thedeposit in another chamber of the same cassette is left intact formicroscopic observation. Alternatively, different dispensing receptaclescan be used to hold separate, independent samples (i.e., from differentsources), which can be processed concurrently by the ferrograph 100simultaneously to save time.

It will therefore be seen that the foregoing represents a highlyadvantageous approach to ferrographic analysis, especially for use withbiological materials. The possible uses of the invention set forthherein are but some that can be realized; others will be apparent tothose skilled in the art. The terms and expressions employed herein areused as terms of description and not of limitation, and there is nointention, in the use of such terms and expressions, of excluding anyequivalents of the features shown and described or portions thereof, butit is recognized that various modifications are possible within thescope of the invention claimed.

What is claimed is:
 1. A ferrograph comprising: a deposition cassettedefining a flow chamber having an inlet port, an outlet port and adeposition surface between said ports; a fluid reservoir in direct fluidcommunication with the inlet port; a source of priming fluid; fluidtransport means connected between said source and the outlet port, saidfluid transport means including pumping means for pumping priming fluidfrom said source through said flow chamber in a fist direction into saidreservoir to establish a meniscus therein; means for introducing asample fluid potentially containing a magnetic material displayingmagnetic properties into said reservoir on top of said meniscus; saidfluid transport means also including means for drawing the priming fluidfollowed by the sample fluid from the reservoir through the flow chamberin a second direction opposite to said first direction, and means forproducing a magnetic field within the flow chamber while the samplefluid is flowing therethrough for urging any magnetic material in thesample fluid toward said deposition surface.
 2. The ferrograph definedin claim 1 and further including means for introducing one or moreadditional fluids into said reservoir on top of the uppermost fluid insaid reservoir.
 3. The ferrograph defined in claim 2 and furtherincluding means for controlling the fluid transport means and theintroducing means so that at least one of said one or more additionalfluids flows through the flow chamber in said second direction at afaster rate than the sample fluid.
 4. The ferrograph defined in claim 1wherein the cross-sectional area of said reservoir is larger than thatof said flow chamber.
 5. The ferrograph defined in claim 1 wherein saidflow chamber it is oriented vertically and said reservoir is oriented atan acute angle with respect to the flow chamber.
 6. The ferrographdefined in claim 1 and further including means for controlling the fluidtransport means and the introducing means to maintain the uppermostfluid in said reservoir at a selected level therein while fluid isflowing through said flow chamber in said second direction.
 7. Theferrograph defined in claim 1 and further including means forcontrolling the fluid transport means and the introducing means so thatthe fluid flows at different rates in said first and second directions.8. The ferrograph defined in claim 7 wherein the fluid flow is faster insaid first direction.
 9. The ferrograph defined in claim 1 wherein thefluid transport means include a reversible peristaltic pump or a syringepump.
 10. The ferrograph defined in 1 wherein the deposition cassetteincludes at least one additional flow chamber having an inlet port andan outlet port, there being an additional fluid reservoir, source ofpriming fluid, sample fluid introducing means and fluid transport meansassociated with each additional flow chamber.
 11. A ferrographcomprising a deposition cassette defining a flow chamber having an inletport, an outlet port and a fluid reservoir in fluid communication withthe inlet port; a source of priming fluid; a reversible pump connectedbetween the source of priming fluid and the outlet port for pumpingpriming fluid from said source through the flow chamber in a firstdirection into the reservoir to establish a meniscus therein; means forintroducing a sample fluid potentially containing a material havingmagnetic properties into said reservoir on top of the meniscus; meansfor reversing the pump so as to draw priming fluid followed by thesample fluid from the reservoir through the flow chamber in a seconddirection opposite to said first direction, and means for producing amagnetic field within the flow chamber while sample fluid is flowingtherethrough in said second direction.
 12. The ferrograph defined inclaim 11 wherein the pump is a peristaltic pump.
 13. The ferrographdefined in claim 11 wherein the pump and the source of priming fluidtogether constitute a syringe.
 14. The ferrograph defined in claim 11wherein the introducing means comprise a supply of sample fluid in fluidtight communication with said reservoir so that when said pump drawspriming fluid from said flow chamber, sample fluid is drawn from saidsupply into said reservoir.
 15. A ferrograph comprising a depositioncassette defining a flow chamber having an inlet port, an outlet portand a deposition surface between said ports; a reservoir in fluidcommunication with the inlet port; means for advancing a priming fluidin a first direction through the outlet port into said flow chamber andthen out the inlet port into said reservoir so as to form a meniscus insaid reservoir; means for adding a sample fluid potentially containing amaterial having magnetic properties to said reservoir in contact withthe meniscus so as to form an interface between the priming fluid andthe sample fluid; means for moving the sample fluid from the reservoirin a second direction opposite to said first direction through said flowchamber and then out said outlet port so as to displace the primingfluid from the flow chamber, and means for producing a magnetic fieldwithin the flow chamber while the sample fluid is flowing therethroughso as to urge any magnetic material in the sample fluid toward saiddeposition surface.